GLYCOLYSIS

Dr. N. C. Baruah
Course content: Metabolism (Study of cycle/pathways without chemical structures) Metabolism of
Carbohydrates: Glycolysis, TCA cycle and glycogen metabolism, regulation of blood glucose level.
Diseases related to abnormal metabolism of Carbohydrates

Glycolysis means lysis of sweet sugar. The sweet sugar is Glucose and lysis is the breakdown
(catabolic degradation).
Glycolysis is the catabolism of glucose in the biological system by a series of enzyme catalysed
reactions, which generate energy in the form of production of Adenosine Triphosphate (ATP).
Glycolysis is a sequence of biochemical reactions for converting glucose(6C) to pyruvate(3C) or
lactate (3C), with the production of energy in the form of ATP and NADH.
Glucose is the primary source of energy. It is obtained by digestion of carbohydrate diet or obtained
from other than carbohydrate sources. It is stored as glycogen in liver and muscles for future use.
Glucose itself cannot pass through the membrane of the cells. It is transported by two transport
systems. One is ATP-independent transport system and another is ATP-dependent transport system.

A healthy adult person requires 1920 to 2900 kcal of energy per day depending on his daily activity.
Human being gets this energy from carbohydrate, fats and proteins. Generally, 40-60% of total energy
is obtained from carbohydrate, 30-40% from fats and 10-15% from proteins.
The excess intake of food than the required amount for expenditure, is stored in the muscles, liver
and adipose tissues in the form of glycogen, fat or triglycerides respectively resulting obesity.
Adenosine diphosphate (ADP) + Pi + En Adenosine triphosphate
Energy is released when ATP is hydrolysed.
ATP is utilised for various function within the cells, in transporting biomolecules across the
membranes, bio-signalling, circulation of blood, muscle contraction for various activities including
locomotion, body movements.
Glycolysis:
Glycolysis occurs in all tissues that oxidise glucose to produce energy as ATP. All sugars obtained
from diet and the sugars by catalytic degradation of glycogen or by gluconeogenesis, transform to
glucose.
Glucose is a Penta hydric aldohexose (6C) and is a dextrorotatory isomer, known as Dextrose. All the
intermediates of glycolysis are also D-isomers. D-sugars indicate that the last but one carbon of the
sugar molecules have absolute configuration similar to D-Glyceraldehyde.
In glycolysis one six carbon glucose (6C) is converted to two molecules of three carbon pyruvate
(3C). To breakdown one six carbon Glucose into two three carbon units of pyruvate, the glucose needs
to be transformed into fructose 1,6-bisphosphate, a high energy molecule. The high energetic doubly
phosphorylated fructose breaks into two three carbon chain compound Glyceraldehyde-3-phosphate.
The glycolysis is a 10-step process of Glucose degradation or metabolism. The first five steps of the
glycolysis are called preparatory phase or energy investment phase.
Preparatory Phase:
In this preparatory phase the two phosphate groups are added to two hydroxyl groups of the glucose
molecule. As the glucose has an aldehyde functional group in the first carbon that is why 1st phosphate
group is added to the hydroxyl group at 6th carbon to make glucose 6-phosphate; which is then
transformed or isomerised to a fructose-6-phosphjate. Fructose has hydroxyl groups at both the end,
so the 2nd phosphate group is introduced to the hydroxyl group of the 1st carbon, which then becomes
Fructose-1,6-bisphosphate. The phosphate groups are donated by ATP molecules and kinases are the
enzymes, namely the Hexokinase at step-1 and phosphofructokinase at the 3rd step.
In the 4th step the Fructose 1,6-bisphosphate is broken down to one three carbon aldehyde, the
Glyceraldehyde-3-phosphate (3C) and one three carbon Dihydroxyacetone phosphate (3C). In the 5th
step the Dihydroxyacetone phosphate is isomerised to Glyceraldehyde-3-phosphate (3C), thus two
glyceraldehyde-3-phosphate are produced.
That results in total two molecules of Glyceraldehyde-3-phosphate.
That is, one six carbon Glucose (6C) molecule has been converted to two three carbon
Glyceraldehyde-3-phosphate (3C) at the expense of two ATP in the preparatory phase.
After the two Glyceraldehyde-3-phosphate formation, the next five steps of glycolysis are the
oxidation, known as the payoff phase. In the payoff phase both the two glyceraldehyde 3-phosphate
are converted to pyruvate, that has a ketone group at the 2nd carbon. This payoff phase release four
ATP molecules or there is a net production of two ATP molecules for each molecule of Glucose
converted to two pyruvates in the complete glycolysis process. The enzymes that produce ATP
molecule are the kinases, the phosphoglutarate kinase in step7 and pyruvate kinase at step 10.

The Payoff phase:

In the 6th step of glycolysis, the Glyceraldehyde-3-phosphate is first converted to 1,3-

Bisphosphoghlycerate by the inorganic phosphate and two NAD+ (differs from the Fructose 1,6-
Bisphosphate formation in the preparatory phase).
In the 7th step, the 1,3-Bisphosphoghlycerate is dephosphorylated to 3-phosphoghlycerate, which is
converted to 2-phosphoghlycerate in the 8th step.
In the 9th step a double bond is inserted in the 2-phosphoghlycerate to convert it to
Phosphoenolpyruvate. In the final step of the anaerobic glycolysis, i.e. in the 10th step, the
Phosphoenolpyruvate is converted to Pyruvate by detaching the phosphate group to form ATP.
 The process of Glycolysis can be represented as a Chart as follows:

Enzymes
Preparatory Phase Glucose

ATP Hexokinase or
① glucokinase
ADP

Glucose-6-phosphate

Phosphohexose
isomerase
②

Fructose-6-phosphate

ATP ③ Phosphofructokinase
ADP

Fructose-1,6-bisphosphate

④ Aldolase

Glyceraldehyde-3-phosphate (3C) Dihydroxyacetone phosphate

+

⑤ Phosphotriose isomerase
(2) Glyceraldehyde-3-phosphate
NAD+
Glyceraldehyde 3-phosphate dehydrogenase
+ ⑥
NADH + H
1,3-Bisphosphoglycerate
Payoff Phase
ADP
Phosphoglycerate kinase
ATP ⑦
3-Phosphoglycerate

Phosphoglycerate mutase
⑧
2-Phosphoglycerate

Enolase
⑨
Phosphoenolpyruvate
ADP Pyruvate kinase
⑩
ATP
Pyruvate